Thrombosis Update最新文献

Hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor-T (CAR-T) immunotherapy are widely used for the management of hematological malignancies. HSCT can be complicated by endothelial injury syndromes, such as HSCT-thrombotic microangiopathy (HSCT-TMA) and sinusoidal obstructive syndrome/veno-occlusive disease (SOS/VOD), which are life-threatening. Moreover, venous thromboembolic events (VTEs) are common in HSCT recipients due to endothelial injury, use of central venous catheters, prolonged hospitalization, and the development of a procoagulant state. VTEs have also been reported post-CAR-T infusion. The management of thrombotic events in these patients is challenging, due to the high risk of bleeding that is present. CAR-T immunotherapy might be followed by toxicities, such as cytokine release syndrome (CRS) and immune effector cell-associated neuro-toxicity syndrome (ICANS). Endothelial dysfunction is implicated in the pathogenesis of these syndromes. Early recognition and management of the above complications are crucial for better patient outcomes.

Heparin-induced thrombocytopenia (HIT) is a rare but severe prothrombotic disorder that develops in patients exposed to heparin products. Diagnosis is associated with significant morbidity and mortality. The mainstay of treatment for HIT involves discontinuing all heparin products and administering non-heparin anticoagulants. Since the publication of the American Society of Hematology (ASH) guidelines in 2018, factor Xa inhibitors have become an attractive alternative. We systematically reviewed the literature to determine the efficacy and safety of factor Xa inhibitors in managing HIT. We included any case series, retrospective, or prospective study that evaluated the efficacy of factor Xa inhibitors. We searched PubMed, Ovid, Embase, Cochrane Central Register of Controlled Trials, and Google Scholar from inception to September 2023. Three reviewers independently reviewed titles, abstracts, and full-text articles to determine eligibility using prespecified inclusion and exclusion criteria. Disagreements were resolved by discussion and consensus. Nine hundred sixty-four articles were screened against title and abstract, and 75 studies were selected for full-text review. Fifteen studies eventually met the inclusion criteria. Two hundred eighty-five patients across 15 studies were treated with factor Xa inhibitor. Across all study arms combined, HIT thrombosis-associated mortality was 0 % (n = 0), recurrent thrombosis was 4.56 % (n = 13), and major bleeding was 2.80 % (n = 8). Factor Xa inhibitors showed positive outcomes in HIT in terms of both safety and efficacy. Major limitation of this review is that the studies included are primarily retrospective and, thus, are subject to inherent limitations of observational study design. More randomized controlled trials (RCT) or prospective studies examining non-inferiority or superiority of transitioning to direct oral anticoagulant (DOAC) vs primary treatment with DOAC are needed.

Background

Nitrous oxide (N₂O), often known as "laughing gas," ranks as a widely used recreational drug among young people in the UK, with 3.9 % of young adults aged 16–24 reporting its use in 2021–2022. Besides its known neurological risks, there is emerging evidence linking N₂O misuse to serious haematological issues, including arterial and venous thrombosis.

Aims/objectives

The project aimed to elucidate the prevalence of N₂O usage in young adults (18–35 years) with unprovoked venous thromboembolism (VTE) between January 2021 and July 2023.

Method

Patient records from three East London emergency departments (ED), coded with a SNOMED code for VTE upon ED discharge between January 2021 and June 2023, were compiled using Qliksense. The data extracted from electronic patient records (EPR) encompassed demographics, confirmed cases of VTE at discharge, and history of N₂O usage. Criteria for exclusion included age restrictions, established provoking factors for VTE, and unconfirmed reports of N₂O use.

Results

We found 26 patients, out of which 8 patients (31 %) reported N₂O use. Among these, a majority of 7 patients (88 %) reported regular N₂O at the time of admission for VTE. Furthermore, 6 patients (75 %) reported regular N₂O use for at least 12 months. The quantity of N₂O usage varied widely, ranging from 7 to 210 (mean = 61.9, ∼495g) small canisters per week with each canister containing 8 g of N₂O. The duration of N₂O use varied significantly ranging from 7 to 59 months (mean = 29.25). This group of young adults (18–35; mean = 25) was 88 % male and 12 % female. The ethnic distribution among the cohort was 62 % Asian or Asian British, 25 % Black or Black British, and 12 % White. Stratified by the index of multiple deprivation 25 % were in quintile 1–2, 50 % were 3–4, 12 % were 5–6, and 12 % were in 7–8 range (0 % 9–10).

Conclusion

Healthcare providers, particularly those in Acute Medicine and EDs, should consider implementing VTE screening protocols for young adults aged 18–35 presenting to ED with reported N₂O misuse and neurological problems. A thorough assessment of N₂O usage patterns is essential, alongside the provision of culturally sensitive health education that addresses the unique needs of marginalised communities. Ongoing research is necessary to elucidate the pathophysiological pathways connecting N₂O use to VTE incidents, particularly its link to increased homocysteine levels.

Cancer-associated thrombosis is a common problem in cancer patients and one of the leading causes of death in this population. Randomised clinical trials have shown that both low-molecular-weight heparins and direct oral anticoagulants are the treatments of choice for cancer-associated thrombosis. Despite this, small sample sizes, poor representation of some patient subgroups and lack of information about real-world clinical situations are some of the limitations of randomised trials. To overcome these problems, registries have been established to collect real-world data from patients with cancer-associated thrombosis, offering new evidence and information to supplement the findings of randomised clinical trials. However, few registries have focused exclusively on cancer patients, and some have excluded various subgroups of patients. Additionally, data collection and processing are another major challenge in analysing registry results, where the emergence of artificial intelligence will play a fundamental role.

Background

Gonadal vein thrombosis (GVT) is an uncommon condition that has been associated with different risk factors (e.g., post-partum period, cancer, recent pelvic surgery, etc.). The optimal management of GVT remains unclear. We sought to assess the efficacy and safety of anticoagulation therapy in adult patients with GVT.

Methods

A systematic search of MEDLINE, EMBASE and PubMed, from inception to February 2023 was performed. The primary efficacy outcome was recurrent venous thromboembolism (VTE). Bleeding outcomes were assessed in the form of major and clinically relevant non-major bleeding (CRNMB) events. Incidence rates of the outcomes were pooled using the random effects model and expressed as event per 100 patient-years with its associated 95 % confidence intervals (CI) using R software.

Results

A total of 14 observational studies and one randomized controlled trial (1134 patients) with GVT met the inclusion criteria and were included in the review. Overall, 429 (37.8 %) patients were treated with anticoagulation. The rate of recurrent VTE was 3.1 per 100 patient-years (95 % CI, 1.6–6.3). The rate of major bleeding and CRNMB events were 1.0 (95 % CI; 0.2–4.5) and 9.9 (95 % CI; 2.6–37.8) per 100 patient-years, respectively.

Conclusion

Gonadal vein thrombosis seems to be associated with a relatively low risk of recurrent VTE and bleeding complications. The risk benefit ratio of anticoagulant therapy remains unclear in this patient population.

Venous thromboembolism (VTE) comprises deep vein thrombosis (DVT) and pulmonary embolism (PE). Acute PE is associated with significant morbidity and mortality. Hospital admission is a common cause of VTE.

We present a complex case of a young female patient who sustained a right tibial plateau fracture following a traumatic, hyperextension knee injury. The patient was admitted by the orthopaedic team for an open reduction and internal fixation and commenced on prophylactic low molecular weight heparin. Post-operatively, the patient became hypoxic, and computed tomography pulmonary angiogram confirmed bilateral large volume pulmonary emboli with evidence of right heart strain. Following review by the pulmonary embolism response team (PERT), the patient was stratified into an intermediate-high risk group, and received unfractionated heparin, however, remained tachycardic and hypoxic with rising lactate levels. Owing to relative contraindications to systemic thrombolysis, the patient underwent catheter-based thrombectomy and inferior vena cava filter placement. The patient improved dramatically over the course of her admission and was later discharged, asymptomatic from a cardiopulmonary standpoint. In hospitalised patients, early VTE risk assessment and prompt initiation of appropriate thromboprophylaxis are crucial in preventing hospital-acquired VTE (HAVTE). However, in instances of HAVTE in complex patients, a well-coordinated multidisciplinary PERT is necessary to consider alternative strategies for managing intermediate to high-risk PE.

Introduction

Pulmonary embolism (PE) probability assessment relies on clinical scoring systems, which have limitations for certain patient populations. We aimed to investigate the use of laboratory values for PE probability assessment.

Materials and methods

This retrospective single-center observational study included patients with suspected PE. Nineteen variables were examined. Logistic regression analysis adjusted for confounding factors was performed, and significant variables were used to develop a scoring method. Receiver operating characteristic (ROC) curves were used to detect PE and determine the optimal cutoff value. Well's scores were also estimated.

Results

The model achieved an accuracy of 84.6 %. Hypocapnia, fever, alkaline phosphatase (ALP), D-dimer, and lactate levels had predictive values. The slope was negative for hypocapnia, ALP, and lactate, and positive for fever and D-dimer levels. Fever, with an adjusted odds ratio (OR) of 1.995, received a score of 2 for values above the cutoff, whereas the remaining variables were assigned a score of 1. Patients with PE had significantly higher scores (mean ± SD: 2.07 ± 0.91) than those without PE (1.80 ± 1.13; P = 0.001). The area under the ROC curve was 0.585 (95 % confidence interval: 0.563–0.606; P = 0.001). Using a cutoff score of 1.5 based on the maximum Youden's index, the scoring system achieved a sensitivity of 73.1 % and specificity of 43.4 %. The Well's score demonstrated a sensitivity of 51.1 % and specificity of 75.1 %.

Conclusion

This study showed statistically significant laboratory values for the probability assessment of PE and the tentative scoring system (PAPEL score). Larger prospective multicenter studies are required to validate this scoring method in a wider population.

Introduction

Oral anticoagulant therapy comes at the cost of a significant bleeding risk. However, it is hard to predict which patients are at risk of major bleeding. Previously we found associations of Calibrated Automated Thrombinography (CAT) parameters obtained in the presence of TIX-5 (an inhibitor of the FV activation by FXa), and plasma levels of TFPIα, γ’-fibrinogen and soluble thrombomodulin with major bleeding in the BLEEDS cohort, a cohort especially powered to find new biomarkers of major bleeding during VKA therapy.

Methods

To determine and compare the predictive capability for major bleeding in the BLEEDS cohort of the above biomarkers, also in a combined model with clinical risk factors, we performed Univariable Prentice-weighted Cox regression analyses and Bayesian variable selection.

Results

The highest predictive value among the laboratory measures were found for thrombin generation lagtime in the presence of TIX-5 (TIX-5 lagtime per 25% increase, hazard ratio (HR) 1.11, 95%CI 1.04–1.18, p=0.001) and full-length tissue factor pathway inhibitor (TFPIα) (per 25% increase HR 1.12, 95%CI 1.03–1.21, p=0.008), which remained significant after correction for multiple testing, and independently associated with major bleeding after Bayesian variable selection. Only the addition of TIX-5 lagtime to the clinical risk factors improved prediction of major bleeding significantly (p<0.001).

Conclusion

We established predictive value of the lagtime of thrombin generation measured in the presence of TIX-5 for the risk of a major bleeding of patients on VKA therapy.